Background: Nature has been a source of medicinal treatments since millennia and plant-based systems continue to play an essential role. Aim: To study the antimicrobial and antibiofilm effect of cranberry on Streptococcus mutans and Lactobacillus acidophilus. Materials and methods: The ethanolic extract of cranberry was tested against standard MTCC strains of S. mutans (MTCC 25175) and L. acidophilus (MTCC 8129) for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The time kill assay was performed to check the time-dependent bactericidal effect of the cranberry extract on microorganisms. Percentage of cell adhesion and biofilm inhibition of the dental microorganism at various doses of cranberry extract was measured by a spectrophotometer and biofilm morphology characteristics were observed under scanning electron microscopy. All the tests were carried out in triplicates. Data were computed in the SPSS software and mean/SD was determined. The results are presented in a descriptive manner; Kruskal–Wallis analysis of variance (ANOVA) and the Friedman's test were applied for comparative evaluation of the groups. p value <0.05 was considered statistically significant. Results: The results showed that MICs of cranberry extract against S. mutans and L. acidophilus are 12.5 mg/dL and 6.125 mg/dL, respectively, and MBCs are 25 mg/dL and 12.5 mg/dL, respectively. A significant decrease in the biofilm formation and cell adhesion of microorganisms at MIC (50%) and MBC (70%) was observed as compared to control as observed under a spectrophotometer and a scanning electron microscope. Conclusion: This study has identified bactericidal, bacteriostatic, and antibiofilm effects of cranberry extract against S. mutans and L. acidophilus in a time-dependent and dose-dependent manner.